Cyclophosphamide
N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Also known as: Cytoxan · Neosar · Procytox · Endoxana · CPM · CTX · B-518 · ciclofosfamida · cyclophosphamidum · cyclophosphanum · NSC-26271 · WR-138719 · Cytophosphane
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| To inhibit local recurrence in dogs with incompletely resected soft tissue sarcomas | 10 mg/m2 PO once daily with piroxicam at 0.3 mg/kg PO once daily | PO | q24h | Continuous (metronomic) | 🌎 NA |
| Antineoplastic | 50 mg/m2 PO 4 days/week OR 250 mg/m2 PO once every 3 weeks OR 100-300 mg/m2 IV weekly | PO/IV | Varies | Protocol dependent | 🌎 NA |
| Immunosuppressant (IMHA/ITP) | 50 mg/m2 PO every 2nd day | PO | q48h | Adjust to manage side effects | 🌎 NA |
| Immunosuppressant (IMHA pulse therapy) | 50 mg/m2 PO daily for 4 days on, 3 days off | PO | Pulse | Ongoing | 🌎 NA |
| Polyarthritis | 1.5 mg/kg (>30 kg), 2 mg/kg (15-30 kg), 2.5 mg/kg (<15 kg) PO daily on 4 consecutive days each week | PO | 4 days/week | 2-4 months (max 4 months) | 🌎 NA |
| Glomerulonephritis | 2.2 mg/kg PO q24h for 4 days, discontinue for 3 days and then repeat | PO | Pulse | Ongoing | 🌎 NA |
| Lymphoma (COP low dose protocol - Induction) | 50 mg/m2 | PO | alternate days OR first 4 days of each week | First 2 months | 🌍 EU |
| Lymphoma (COP low dose protocol - Maintenance after 2 months) | 50 mg/m2 | PO | alternate days OR first 4 days of each second week | Months 2 to 6 | 🌍 EU |
| Lymphoma (COP low dose protocol - Maintenance after 6 months) | 50 mg/m2 | PO | q48h (one week in three) OR first 4 days of each third week | Months 6 to 12 | 🌍 EU |
- To inhibit local recurrence in dogs with incompletely resected soft tissue sarcomas: If unacceptable adverse effects develop, increase interval to every other day.
- Antineoplastic: Consult veterinary oncologist.
- Immunosuppressant (IMHA/ITP): Used with glucocorticoids.
- Immunosuppressant (IMHA pulse therapy): Alternatively 50 mg/m2 PO every other day.
- Polyarthritis: Given with prednisolone.
- Lymphoma (COP low dose protocol - Induction): Co-administer with 1 mg/kg furosemide q12h on treatment days to reduce cystitis risk.
- Lymphoma (COP low dose protocol - Maintenance after 2 months): Alternate-week therapy.
- Lymphoma (COP low dose protocol - Maintenance after 6 months): Stop and monitor for relapse after 12 months.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Immunosuppressant (ITP or IMHA) | 50 mg/m2 PO every 2nd day | PO | q48h | Ongoing | 🌎 NA |
| To slow progression of FIP | 2-4 mg/kg PO four times a week | PO | 4 times/week | Ongoing | 🌎 NA |
- Immunosuppressant (ITP or IMHA): Author prefers cyclosporine or chlorambucil in cats.
Small Mammals
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Antineoplastic (lymphoma) in rabbits | 50 mg/m2 PO daily for 3 days each week OR 100-200 mg/m2 IV every 7 days | PO/IV | Varies | Protocol dependent | 🌎 NA |
- Antineoplastic (lymphoma) in rabbits: Consider fully implantable vascular access device for IV.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Neoplastic diseases | 200 mg/m2 (usually 1 gram per horse per dose) IV every 1-2 weeks | IV | q1-2 weeks | Protocol dependent | 🌎 NA |
- Neoplastic diseases: Consult veterinary oncologist.
Sheep
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Chemical shearing agent | Historical use | PO/IV | Single | Single | 🌎 NA |
- Chemical shearing agent: Historical use only.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Cyclophosphamide is a potent antineoplastic and immunosuppressive agent used widely in veterinary medicine for dogs and cats.
- Antineoplastic Use: Employed in combination protocols for lymphomas, leukemias, carcinomas, and sarcomas. Low-dose metronomic (continuous) therapy is also utilized to prevent sarcoma recurrence.
- Immunosuppressive Use: Used for severe immune-mediated diseases such as systemic lupus erythematosus (SLE), immune-mediated thrombocytopenia (ITP), immune-mediated hemolytic anemia (IMHA), and pemphigus.
Clinical Pearl: Cyclophosphamide is cell-cycle phase nonspecific. Because it is a prodrug requiring hepatic activation, it is not a vesicant and can be given safely via peripheral veins, unlike many other chemotherapy agents.
Mechanism of action
Cyclophosphamide is a prodrug that is metabolized in the liver by cytochrome P450 enzymes into active metabolites, primarily phosphoramide mustard and acrolein.
Phosphoramide mustard → acts as an alkylating agent → forms cross-links within and between DNA strands → interferes with DNA replication and RNA transcription → triggers apoptosis and cell death.
Acrolein is a toxic byproduct that concentrates in the urinary bladder and is responsible for sterile hemorrhagic cystitis. The drug also profoundly suppresses B-cell and T-cell function, leading to its immunosuppressive effects.
Safety & warnings
Contraindications
- Prior anaphylactic reactions to the drug
- Severe pre-existing myelosuppression (leukopenia, thrombocytopenia)
- Active infections where immunosuppression may be dangerous
- No specific contraindications available in the monograph, but clinically contraindicated in patients with severe pre-existing myelosuppression or active haemorrhagic cystitis.
- Pre-existing severe myelosuppression
Adverse effects
- Myelosuppression (leukopenia, thrombocytopenia, anemia)
- Gastroenterocolitis (anorexia, nausea, vomiting, diarrhea)
- Sterile hemorrhagic cystitis (induced by acrolein metabolite)
- Alopecia (especially in continuously growing coats like Poodles and Old English Sheepdogs)
- Pulmonary infiltrates and fibrosis
- Hyponatremia
- Secondary leukemia
- Myelosuppression (nadir usually 5-14 days post-therapy)
- Sterile haemorrhagic cystitis (caused by acrolein metabolite)
- Bladder fibrosis
- Transitional cell carcinoma (secondary to chronic cystitis)
- Diarrhoea
- Hepatotoxicity
- Nephrotoxicity
- Reduction in hair growth rate / Alopecia
- Gastrointestinal toxicity
Precautions
WARNING: Cyclophosphamide is potentially teratogenic and embryotoxic. Safe use in pregnancy is not established.
- Hemorrhagic Cystitis: Up to 30% of dogs on long-term therapy may develop sterile hemorrhagic cystitis. Encourage frequent urination and water intake. Co-administration of furosemide may reduce risk.
- Myelosuppression: Monitor CBC closely. Delay doses if severe leukopenia or thrombocytopenia occurs.
- Handling: Cytotoxic precautions must be taken. Do not split or crush tablets. Avoid direct contact with urine or feces of treated animals.
Drug interactions
May increase the myelosuppression caused by cyclophosphamide
Potentiation of cardiotoxicity may occur
May inhibit cyclophosphamide metabolism
May increase the rate of metabolism to active metabolites, increasing toxicity risk
May increase the myelosuppression caused by cyclophosphamide
Metabolism may be slowed, prolonging effects due to decreased pseudocholinesterases
Absorption of orally administered digoxin may be decreased (may occur several days after dosing)
Increase cyclophosphamide toxicity due to increased rate of conversion to metabolites
Reduce cyclophosphamide efficacy
Reduce cyclophosphamide efficacy
Insulin requirements are altered by concurrent cyclophosphamide
Inhibits hepatic cytochrome P450 enzyme pathway, potentially altering the metabolism and increasing toxicity of chemotherapeutics.
Monitoring
- Efficacy (tumor response or remission of immune-mediated disease)
- Complete Blood Count (CBC) regularly for myelosuppression (nadir typically 7-14 days)
- Urinalysis regularly for signs of sterile hemorrhagic cystitis (hematuria)
- Uric acid levels (blood and urine)
- White Blood Cell (WBC) count (regular monitoring recommended due to myelosuppression)
- Urinalysis (monitor for haematuria indicating sterile haemorrhagic cystitis)
- Renal and hepatic function panels
- Free-catch urine by dipstick prior to and each week of treatment
- Haematology
- Biochemistry (prior to first treatment and minimum every 6 months)
Pharmacokinetics
Half-life
Absorption
Well absorbed after oral administration with peak levels occurring about 1 hour after dosing.
Distribution
Distributed throughout the body, including CSF (subtherapeutic levels). Minimally protein bound. Distributes into milk and crosses the placenta.
Metabolism
Metabolized in the liver to several active and inactive metabolites (including phosphoramide mustard and acrolein).
Elimination
Majority of the drug is excreted as metabolites and unchanged drug in the urine.
Overdose
Limited information on acute overdoses. The lethal dose in dogs is reported as 40 mg/kg IV.
If an oral overdose occurs, perform gut emptying (emesis/lavage) if indicated and hospitalize the animal for aggressive supportive care, including IV fluids to flush the bladder and prevent hemorrhagic cystitis.
Available products
Formulations
- Oral tablets
- Powder for injection
- Compounded oral elixir/suspension
- Injectable: 100 mg, 200 mg, 500 mg, 1000 mg powder for reconstitution
- Oral: 50 mg tablets
Human-labeled
- Cyclophosphamide Tablets: 25 mg & 50 mg
- Cyclophosphamide Powder for Solution for Injection: 500 mg, 1 g and 2 g
- Endoxana 50 mg tablets
- Endoxana 100 mg, 200 mg, 500 mg, 1000 mg powder for reconstitution
Regulatory status
Often requires compounding by specialized pharmacies (e.g., ChemoPet) for accurate veterinary dosing.
Often requires compounding by specialized pharmacies (e.g., ChemoPet) for accurate veterinary dosing.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store tablets and powder for injection at <25°C (brief excursions up to 30°C permitted). Store tablets in tight containers. Reconstituted injection is stable for 24 hours at room temperature or 6 days refrigerated. Compounded oral elixir is stable for 14 days refrigerated.
Client information
Important Safety Warning: This is a potent chemotherapy drug. Follow all handling instructions carefully.
- Handling: Do not break or crush tablets. Wash hands thoroughly after handling. Avoid direct contact with your pet's urine, feces, or vomit while they are on this medication.
- Urination: Take your dog for frequent walks to encourage urination, especially in the morning. This helps prevent bladder irritation.
- When to call the vet: Contact your veterinarian immediately if you notice blood in the urine, straining to urinate, abnormal bleeding, bruising, severe lethargy, vomiting, or diarrhea.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.